Liver-specific knockout of B cell lymphoma 6 suppresses progression of non-alcoholic steatohepatitis in mice
Liver-specific knockout of B cell lymphoma 6 suppresses progression of non-alcoholic steatohepatitis in mice
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DOI：
10.1038/s41598-020-66539-z
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发表时间：
2020-06-16
影响因子：
4.6
通讯作者：
Kamiya, Akihide
中科院分区：
文献类型：
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作者：
Chikada, Hiromi;Ida, Kinuyo;Kamiya, Akihide
非酒精性脂肪性肝炎（NASH）的患病率随着代谢紊乱（如血脂异常、高血压和高脂血症）而迅速增加。B细胞淋巴瘤6（Bcl 6）是一种转录抑制因子，对生殖中心B细胞的形成至关重要。在这项研究中，我们分析了Bcl 6在NASH进展相关的病理变化中的作用，如肝脏脂质积聚，肝纤维化和肝癌发生。使用肝脏特异性Bcl 6敲除（Bcl 6-LKO）和对照野生型（WT）小鼠分析Bcl 6在NASH中的作用。通过用胆碱缺乏、L-氨基酸限定的高脂饮食（CDAHFD）喂养小鼠来建立小鼠NASH模型。用CDAHFD喂养WT小鼠7周诱导形成类似于人NASH的组织病理学特征，如肝脂质积聚、肝细胞损伤和纤维化。这些组织病理学变化在Bcl 6-LKO小鼠中显着减弱。此外，用CDAHFD喂养雄性WT小鼠38周诱导肝肿瘤的形成，这在Bcl 6-LKO小鼠中被抑制。这些发现表明Bcl 6参与NASH和NASH衍生肿瘤的进展。
The prevalence of non-alcoholic steatohepatitis (NASH) rapidly increases with metabolic disorders such as dyslipidaemia, high blood pressure, and hyperglycaemia. B cell lymphoma 6 (Bcl6), a transcriptional repressor, is essential for the formation of germinal centre B cells. In this study, we analysed the role of Bcl6 in NASH progression-associated pathological changes, such as hepatic lipid accumulation, liver fibrosis, and hepatocarcinogenesis. The roles of Bcl6 in NASH were analysed using liver-specific Bcl6 knockout (Bcl6-LKO) and control wild-type (WT) mice. The murine NASH model was established by feeding the mice with choline-deficient, L-amino-acid-defined, high-fat diet (CDAHFD). Feeding the WT mice with CDAHFD for 7 weeks induced the formation of histopathological features resembling human NASH, such as hepatic lipid accumulation, hepatocellular injury, and fibrosis. These histopathological changes were significantly attenuated in Bcl6-LKO mice. Additionally, feeding the male WT mice with CDAHFD for 38 weeks induced the formation of liver tumours, which was suppressed in Bcl6-LKO mice. These findings indicate that Bcl6 is involved in the progression of NASH and NASH-derived tumours.